The goal of the investigations described in this proposal is to understand more completely the physico-chemical basis of regulation of ion movement across biological membranes. We are particularly interested in the roles of electrical potential differences and chemical agents such as hormones, drugs and toxins in regulating ion transport associated with physiological processes as excitation, propagation and secretion. We propose to use bilayer membranes composed of known lipids to explore the properties of: 1) protein-induced ion conducting channels, 2) carriers, pumps and gated channels and 3) regulation of ion movements by factors related to membrane composition. Projects on protein-induced channels include two which do not involve specific membrane receptors. We will investigate further the properties of channels produced in bilayers by proteolipids. We will also study the voltage-dependent channels that develop in bilayers exposed to hemocyanin. Another project deals with the investigation of the channels produced by the specific interaction between cholera toxin and its membrane receptor. We will also continue to define the relation between the equilibrium and kinetic properties of ion-binding cyclic peptides and their capacity to act as ion carriers across membranes. The third group of projects deals with the influence of interfacial electrical potentials and membrane fluidity on the formation of channels and the movement of lipid soluble ions. In one project, we will explore the effect of cholesterol on the electrical gating of alamethicin channels. In another project, we will investigate the effects of phloretin and its analogues on the interfacial potential and other properties of the bilayer.